Grainger Laboratory

Wnt Signaling in Hematopoietic Stem Cell Development and Cancer

If the human body is an ongoing construction project, then stem cells are its all-purpose building materials. These biological “blank slates” give rise to all the specialized cell types needed to assemble and power the human body, from skin cells to heart cells and everything in between.

This incredible ability to differentiate makes stem cells central players in normal development as well as in diseases like cancer. Understanding exactly how stem cells work — and what happens when the processes that govern stem cell development go awry — holds great promise for better understanding health and developing new treatments for cancer and other diseases. To this end, the Grainger Lab investigates the mechanisms that govern how stem cells are made, how they are maintained and — when things go wrong — how they can become cancerous.

We are particularly interested in the Wnt pathway, a cellular communication channel that is central to a plethora of processes during embryonic development, tissue regeneration and carcinogenesis. In a previous study by our lab (Grainger and Richter, 2016, Cell Reports), we determined that a very specific Wnt signal (Wnt9a) is required for the amplification of hematopoietic stem cells earlier in development than was previously thought. In our follow up study (Grainger, 2019, Nature Cell Biology), we found that the specific Wnt9a signal is received by Fzd9b and that signaling specificity is conferred by the epidermal growth factor receptor (EGFR). We are now working to learn more about this signaling axis.

We’re also interested in how non-canonical Wnt signals arise. Using zebrafish and cell culture as models, we’re investigating if there are specific functions for Wnt ligands or Fzd receptors in stem cell biology.